We propose to decrease the morbidity and mortality associated with severe aplastic anemia by continuing the evaluation of its treatment by marrow grafting using HLA-identical family members as donors. We hope to define the ultimate role of this approach and compare short-and long-term results to those obtained with unrelated marrow grafts and to results without marrow transplantation. Studies will address the problems of graft rejection, acute and chronic graft-host disease (GVHD), and long-term sequelae. During the next grant period, we anticipate, firstly, to evaluate novel GVHD prevention consisting of a combination of mycophenolate mofetil and cyclosporine, and, secondly, to evaluate the usefulness of novel conditioning regimens consisting of monoclonal antibodies to lymphocyte surface determinants as substitute for the traditionally used cyclophosphamide regimen. We will also continue exploring allogeneic marrow transplantation for the treatment of various genetically hematological disorders, including sickle cell-anemia. Finally, we shall explore a new area of investigation, transplantation of allogeneic stem cells as therapy of patients with severe or refractory autoimmune diseases, e.g. scleroderma.